This report describes the meta-analysis of aggregate data on adverse effects of bisphosphonates.
26 studies are considered, which in total reported 112 distinctly-named adverse events. Among these events, there are 102 distinct events for which there is at least one study comparing incidence of that event between a bisphosphonate treatment group and a no-bisphosphonate control group.
For each of these 102 events, the data were analysed in the same way. The methods, and highlighted results, are given in in this document. Extra details for each of these analyses are reported in Appendix 2.
Events might be grouped into categories corresponding to similar physiological systems (as advised by a clinician REF). Here they are analysed independently, though the results are presented in groups.
For each event, there is a different set of trials that reported data on that event, giving a different network of comparisons between treatments. Five alternative models for network meta-analysis are compared, defined by different groupings of treatments. From the finest to the coarsest grouping, these are:
Different doses and delivery methods of different drugs considered as different treatments. The network corresponding to this model is shown as the “full network of comparisons” in Appendix 2.
Different delivery methods considered as different treatments, but different doses of the same drug considered as the same treatment.
Different drugs considered as different treatments, but different doses and delivery methods of the same drug considered as the same treatment.
Nitrogenous bisphosphonates and non-nitrogenous bisphosphonates (just clodronate) considered as different treatments.
All bisphosphonates considered as the same treatment.
Non-bisphosphonate control groups were distinguished as either placebo, observation-only or denosumab.
In two studies, treatment arms are distinguished by the different hormone therapies given. These are modelled in the same way as different doses of the same drug. (In Appendix 2, the arm given a hormone therapy that is not an aromatase inhibitor is labelled “notai”).
A network meta-analysis model was obtained for each event using the following procedure. This procedure aims to find the best-fitting model which uses all potentially-relevant data, which requires a “connected network” of treatments.
If the treatment network is disconnected under the finest model (grouping 1), but becomes connected when placebo and observation-only controls are considered to be the same treatment, then these two control groups are considered to be the same. Otherwise these controls are separated.
Starting with the finest model (grouping 1), the treatments are grouped until the resulting treatment network is connected.
All network meta-analysis models ranging from the finest connected model to the coarsest are fitted.
The optimal model is selected from among those which fitted successfully, using the deviance information criterion (DIC REF), a measure of model fit or predictive ability. The network diagram for the selected model is shown in Appendix 2.
If no network meta-analysis model fitted successfully, then the results for that event are reported from direct-data meta-analysis only. Unsuccessful fits are generally due to sparsity of information.
Technical details of the network meta-analysis models, and the model comparison and checking procedure, are reported in Appendix 1.
For the selected model, a corresponding classical meta-analysis is also performed based on the direct comparisons alone.
## Warning in GGally::ggnet2(g, label = labels, edge.label = edge.label, edge.size = E(g)$weight, : ggnet2 does not know how to handle self-loops
This table lists the events and treatments for which either the direct comparison or the selected network meta-analysis model produced a practically and statistically significant treatment effect, defined as either
which is also “statistically significant” (lower credible limit greater than 1 for odds ratios, or 0 for risk differences).
The odds ratio is the ratio of the odds of the event between the treatment group (as defined in the table) and an “observation only” control group.
The risk difference is the estimated absolute risk for patients given the active treatment, minus a constant baseline risk. These baseline risks are listed in the table below. For cancer patients they are obtained from classical meta-analysis of the direct data from the “observation-only” arms of the bisphosphonate trials. For “healthy” patients they are obtained from the placebo arm of the NCT00083174 study of exemestane v placebo for postmenopausal women at high risk of breast cancer. The risk differences are (currently) only calculated under the network meta-analysis model.
Where there is no baseline risk / risk difference for healthy women, this is because the event was not reported in the NCT00083174 study. If the baseline risk is close to zero, then the risk difference will also be negligible.
Treatment | Direct OR | NMA OR | Baseline risk (cancer) | Risk difference (cancer) | Baseline risk (healthy) | Risk difference (healthy) | Proportion of graded events that are serious | ||
MYALGIA | |||||||||
MYALGIA | Ibandronate | 2.04 (1.13, 3.85) | 0.03 | 0.03 (0, 0.09) | 0.06 (39/611) | ||||
MYALGIA | Pamidronate | 2.32 (1.09, 5.21) | 0.03 | 0.04 (0, 0.12) | (0/0) | ||||
MYALGIA | Zoledronic_acid | 1.52 (1.31, 1.75) | 2.36 (1.61, 3.6) | 0.03 | 0.04 (0.02, 0.08) | 0.03 (47/1343) | |||
stiffness | Zoledronic_acid_2_IV | 2.72 (1.46, 5.06) | 2.76 (1.27, 5.83) | 0.02 | 0.03 (0, 0.07) | 0 (0/37) | |||
OTHERS | |||||||||
ABDOMINAL PAIN | Bisphosphonate | 1.51 (1.13, 2.02) | 1.51 (1.1, 2.11) | 0.13 | 0.05 (0.01, 0.11) | 0.1 (122/1277) | |||
ARTHRALGIA | Nitrogenous | 1.53 (1.29, 1.81) | 1.54 (1.28, 1.86) | 0.17 | 0.07 (0.04, 0.1) | 0.0000 | 0 (0, 0) | 0.04 (189/5071) | |
BACK PAIN | Nitrogenous | 1.54 (1, 2.37) | 1.64 (1.08, 2.69) | 0.08 | 0.05 (0.01, 0.11) | 0.1 | 0.05 (0.01, 0.13) | 0.03 (37/1247) | |
CARDIAC EVENTS | Nitrogenous | 2.51 (1.52, 4.17) | 2.73 (1.33, 6.31) | 0.03 | 0.04 (0.01, 0.12) | 0.0020 | 0 (0, 0.01) | 0.62 (143/231) | |
CARDIAC EVENTS | Non_nitrogenous | 5.22 (0.25, 109.67) | 4.35 (1.44, 13.6) | 0.03 | 0.08 (0.01, 0.25) | 0.0020 | 0.01 (0, 0.02) | 0.32 (21/65) | |
CHILLS | Zoledronic_acid_IV | 8.55 (2.26, 32.32) | 15.19 (3.96, 94.86) | 0.02 | 0.24 (0.06, 0.66) | 0.01 (3/213) | |||
DIARRHOEA | Non_nitrogenous | 3.34 (1.18, 9.45) | 1.81 (1.35, 2.74) | 0.11 | 0.07 (0.03, 0.14) | 0.03 | 0.03 (0.01, 0.05) | 0.08 (49/591) | |
DYSGEUSIA | Zoledronic_acid_2_IV | 10.1 (1.17, 87.24) | 8.53 (1.25, 119.84) | 0.0010 | 0.01 (0, 0.11) | ||||
FATIGUE | Bisphosphonate | 1.13 (1.02, 1.26) | 1.28 (1.06, 1.65) | 0.1 | 0.03 (0.01, 0.06) | 0.21 | 0.04 (0.01, 0.09) | 0.05 (247/4607) | |
FEVER | Pamidronate_IV | 1.52 (0.47, 4.92) | 4.87 (1.9, 12.62) | 0.01 | 0.05 (0.01, 0.13) | 1 (3/3) | |||
FEVER | Zoledronic_acid_IV | 4.06 (3.06, 5.38) | 5.2 (2.88, 8.79) | 0.01 | 0.05 (0.02, 0.09) | 0.09 (82/933) | |||
HEADACHE | Zoledronic_acid | 1.19 (1.02, 1.4) | 1.48 (1.06, 2.25) | 0.24 | 0.08 (0.01, 0.18) | 0.03 (36/1304) | |||
HEPATOTOXICITY | Clodronate_Oral | 1.69 (1.05, 2.71) | 1.46 (0.78, 2.59) | 0.26 | 0.08 (-0.04, 0.22) | 0.15 (14/95) | |||
HEPATOTOXICITY | Ibandronate_Oral | 4.27 (1.28, 14.22) | 3.39 (1.13, 11.73) | 0.26 | 0.28 (0.02, 0.54) | (0/0) | |||
hypertonia/muscle spasms | Bisphosphonate | 1.53 (1.02, 2.3) | 1.52 (0.93, 2.81) | 0.04 | 0.02 (0, 0.07) | 0.14 (15/106) | |||
HYPOCALCEMIA | Ibandronate | 6.15 (1.16, 41.76) | 0.04 | 0.17 (0.01, 0.6) | 0.02 (5/210) | ||||
HYPOCALCEMIA | Pamidronate | 3.23 (1.45, 7.22) | 3.18 (1.2, 8.64) | 0.04 | 0.08 (0.01, 0.23) | (0/0) | |||
HYPOCALCEMIA | Zoledronic_acid | 7.07 (0.87, 57.56) | 7.28 (1.36, 48.93) | 0.04 | 0.2 (0.01, 0.64) | 0.03 (11/336) | |||
increased bone pain | Bisphosphonate | 1.73 (1.47, 2.04) | 1.79 (1.33, 2.49) | 0.11 | 0.07 (0.03, 0.13) | 0.1 (352/3386) | |||
INFECTION | Ibandronate_Oral | 2.24 (1.18, 4.22) | 0.22 | 0.0009 | (0/0) | ||||
Influenza-like symptoms | Bisphosphonate | 22.18 (2.98, 164.89) | 16.09 (2.04, 207.85) | 0.03 | 0.33 (0.03, 0.85) | 0.05 (35/718) | |||
NAUSEA | Bisphosphonate | 1.21 (1.08, 1.35) | 1.33 (1.11, 1.63) | 0.34 | 0.07 (0.02, 0.12) | 0.05 | 0.02 (0.01, 0.03) | 0.09 (323/3579) | |
NEUROSENSORY PROBLEMS | Bisphosphonate | 1.23 (1.05, 1.45) | 1.29 (1.05, 1.66) | 0.1 | 0.03 (0, 0.06) | 0.0000 | 0 (0, 0) | 0.03 (52/1509) | |
OsteoNecrosis of the Jaw | Nitrogenous | 7.69 (2.31, 25.55) | 0.0050 | (0/0) | |||||
periodontal disease | Zoledronic_acid_2_IV | 15.34 (0.87, 269.36) | 10.2 (1.14, 1322.28) | 0.14 (1/7) | |||||
THROMBOEMBOLIC EVENTS | Clodronate | 7.27 (1.41, 33.44) | 0.02 | 0.11 (0.01, 0.38) | 0.0009 | 0.01 (0, 0.03) | 1 (27/27) | ||
THROMBOEMBOLIC EVENTS | Ibandronate | 13.15 (2.36, 68.93) | 0.02 | 0.19 (0.03, 0.56) | 0.0009 | 0.01 (0, 0.06) | 0.91 (10/11) | ||
THROMBOEMBOLIC EVENTS | Zoledronic_acid | 3.18 (1.34, 7.51) | 2.79 (0.99, 7.42) | 0.02 | 0.03 (0, 0.11) | 0.0009 | 0 (0, 0.01) | 0.72 (28/39) | |
VOMITING | Non_nitrogenous | 1.67 (1.18, 2.92) | 0.19 | 0.09 (0.03, 0.22) | 0.0004 | 0 (0, 0) | 0.03 (9/312) |
Note the reported “treatment” in these tables depends on the selected model - this could refer to all bisphosphonates, or the dose and delivery method of a particular drug, or some categorisation in between. If the selected model distinguishes between doses, the dose categories are labelled with a number.
The same procedure above was followed to select an optimal network meta-analysis model for the data including just studies with “complete” reporting. About half of the events selected above still have significant treatment effects, though perhaps for a slightly different treatment definition. Many are no longer “significant”, and there are some new ones (hypertonia/muscle spasms, dysgeusia, abdominal pain) that become “significant” by some criterion.
Treatment | Direct OR | NMA OR | Baseline risk (cancer) | Risk difference (cancer) | Baseline risk (healthy) | Risk difference (healthy) | Proportion of events that are serious | ||
MYALGIA | |||||||||
MYALGIA | Zoledronic_acid | 3.3 (2.06, 5.28) | 3.22 (1.65, 5.83) | 0.03 | 0.07 (0.02, 0.14) | 0.03 (28/1034) | |||
OTHERS | |||||||||
BACK PAIN | Nitrogenous | 2.19 (0.78, 6.13) | 2.46 (1, 6.6) | 0.08 | 0.1 (0, 0.29) | 0.1 | 0.11 (0, 0.32) | 0.03 (37/1243) | |
CARDIAC EVENTS | Clodronate_1_Oral | 5.22 (0.25, 109.67) | 7.84 (1.27, 33.46) | 0.03 | 0.15 (0.01, 0.45) | 0.0020 | 0.01 (0, 0.05) | 0.32 (21/65) | |
CARDIAC EVENTS | Ibandronate_3_Oral | 12.18 (2.01, 59.73) | 0.03 | 0.22 (0.03, 0.6) | 0.0020 | 0.02 (0, 0.09) | 1 (18/18) | ||
DIARRHOEA | Non_nitrogenous | 3.34 (1.18, 9.45) | 2.91 (1.48, 5.94) | 0.11 | 0.15 (0.04, 0.31) | 0.03 | 0.06 (0.02, 0.14) | 0.08 (42/503) | |
DYSGEUSIA | Bisphosphonate | 7.04 (1.2, 41.3) | 6.26 (0.95, 74.5) | 0.0010 | 0.01 (0, 0.07) | ||||
FATIGUE | Zoledronic_acid_1_IV | 1.94 (1.32, 2.84) | 1.9 (0.96, 3.94) | 0.1 | 0.08 (0, 0.21) | 0.21 | 0.12 (-0.01, 0.3) | 0.01 (19/1335) | |
FATIGUE | Zoledronic_acid_2_IV | 1.76 (1.14, 2.73) | 2.38 (1.22, 5.15) | 0.1 | 0.11 (0.02, 0.27) | 0.21 | 0.18 (0.04, 0.37) | 0 (0/362) | |
FEVER | Clodronate_1_Oral | 6.54 (1.84, 45.74) | 0.01 | 0.06 (0.01, 0.36) | 0.01 (1/83) | ||||
FEVER | Ibandronate_3_Oral | 8.83 (2.48, 60.44) | 0.01 | 0.09 (0.02, 0.42) | 0 (0/70) | ||||
FEVER | Zoledronic_acid_1_IV | 17.55 (4.24, 72.7) | 27.03 (10.19, 179.58) | 0.01 | 0.25 (0.1, 0.69) | 0.05 (28/570) | |||
FEVER | Zoledronic_acid_2_IV | 34.76 (8.48, 142.55) | 30.72 (11.84, 178.43) | 0.01 | 0.27 (0.12, 0.68) | 0.03 (6/192) | |||
FEVER | Zoledronic_acid_4_IV | 6.8 (2.23, 38.99) | 0.01 | 0.07 (0.02, 0.32) | 0.08 (3/37) | ||||
HEADACHE | Zoledronic_acid_IV | 2.19 (1.36, 3.52) | 2.29 (1.32, 3.93) | 0.24 | 0.18 (0.05, 0.31) | 0.02 (22/931) | |||
hypertonia/muscle spasms | Bisphosphonate | 3.68 (1.12, 12.05) | 3.57 (0.94, 22.24) | 0.04 | 0.1 (0, 0.46) | 0.21 (12/58) | |||
HYPOCALCEMIA | Bisphosphonate | 1.6 (1.03, 2.51) | 1.5 (0.76, 2.81) | 0.04 | 0.02 (-0.01, 0.07) | 0.02 (9/502) | |||
increased bone pain | Bisphosphonate | 1.84 (1.37, 2.48) | 1.86 (1.15, 3.08) | 0.11 | 0.08 (0.02, 0.17) | 0.07 (147/2131) | |||
NEUROSENSORY PROBLEMS | Bisphosphonate | 1.56 (1.1, 2.21) | 1.49 (1, 2.23) | 0.1 | 0.04 (0, 0.1) | 0.0000 | 0 (0, 0) | 0.02 (23/1429) | |
NEUTROPENIA | Nitrogenous | 2.04 (0.7, 5.93) | 2.33 (1, 5.43) | 0.04 | 0.05 (0, 0.15) | 0.05 (8/166) | |||
SKIN DISORDER | Bisphosphonate | 1.6 (1.03, 2.48) | 1.48 (0.87, 2.44) | 0.05 | 0.02 (-0.01, 0.06) | 0.03 (37/1142) | |||
THROMBOEMBOLIC EVENTS | Ibandronate | 33.15 (1.62, 474.44) | 0.02 | 0.38 (0.01, 0.88) | 0.0009 | 0.03 (0, 0.3) | 1 (10/10) | ||
THROMBOEMBOLIC EVENTS | Zoledronic_acid | 7.97 (1.4, 45.55) | 4.38 (0.53, 46.06) | 0.02 | 0.06 (-0.01, 0.46) | 0.0009 | 0 (0, 0.04) | 0.67 (18/27) |
The graph below shows all the events for which
a significant odds ratio was highlighted in the main analysis.
no significant odds ratio was detected when studies with incomplete reporting were excluded
The treatment categorisations are shown under the best fitting model in the main analysis. Comparing the red and blue lines shows how the results change when studies with incomplete reporting are excluded.
Table 2 gives odds ratios from direct and selected network meta-analysis models for all events, sorted by clinical category, including non-significant results. Effects significant by either criterion, as listed in Table 1, are shown here in red.
More detailed results, for all 103 events, including network diagrams, raw data and “forest plots” of meta-analysis results, are given in Appendix 2.
Treatment | Direct OR | NMA OR | Baseline risk (cancer) | Risk difference (cancer) | Baseline risk (healthy) | Risk difference (healthy) | ||
MYALGIA | ||||||||
MYALGIA | Clodronate | 1.24 (0.59, 2.6) | 0.03 | 0.01 (-0.01, 0.05) | ||||
MYALGIA | Ibandronate | 2.04 (1.13, 3.85) | 0.03 | 0.03 (0, 0.09) | ||||
MYALGIA | Pamidronate | 2.32 (1.09, 5.21) | 0.03 | 0.04 (0, 0.12) | ||||
MYALGIA | Zoledronic_acid | 1.52 (1.31, 1.75) | 2.36 (1.61, 3.6) | 0.03 | 0.04 (0.02, 0.08) | |||
stiffness | Zoledronic_acid_2_IV | 2.72 (1.46, 5.06) | 2.76 (1.27, 5.83) | 0.02 | 0.03 (0, 0.07) | |||
stiffness | Zoledronic_acid_2notai_IV | 1.28 (0.58, 2.85) | 1.2 (0.47, 3.09) | 0.02 | 0 (-0.01, 0.03) | |||
OTHERS | ||||||||
ABDOMINAL PAIN | Bisphosphonate | 1.51 (1.13, 2.02) | 1.51 (1.1, 2.11) | 0.13 | 0.05 (0.01, 0.11) | |||
ALANINE AMINOTRANSFERASE | Clodronate_1_Oral | 0.15 (0.02, 3.1) | 0.0090 | -0.01 (-0.01, 0.02) | 0.0004 | 0 (0, 0) | ||
ALANINE AMINOTRANSFERASE | Ibandronate_3_Oral | 0.05 (0.01, 1.15) | 0.0090 | -0.01 (-0.01, 0) | 0.0004 | 0 (0, 0) | ||
ALANINE AMINOTRANSFERASE | Ibandronate_4_IVAndOral | 0.05 (0, 2.34) | 0.0090 | -0.01 (-0.01, 0.01) | 0.0004 | 0 (0, 0) | ||
ALANINE AMINOTRANSFERASE | Zoledronic_acid_1_IV | 0.34 (0.01, 8.33) | 0.07 (0.01, 1.38) | 0.0090 | -0.01 (-0.01, 0) | 0.0004 | 0 (0, 0) | |
ALANINE AMINOTRANSFERASE | Zoledronic_acid_2_IV | 0.08 (0.01, 1.98) | 0.0090 | -0.01 (-0.01, 0.01) | 0.0004 | 0 (0, 0) | ||
ALKALINE PHOSPHATASE | Zoledronic_acid_1_IV | 0.45 (0.09, 2.22) | 0.15 | 0.0000 | ||||
ALKALINE PHOSPHATASE | Zoledronic_acid_2_IV | 0.26 (0.05, 1.33) | 0.15 | 0.0000 | ||||
ALLERGIC REACTIONS | Zoledronic_acid | 3.27 (0.13, 83.03) | 0.29 (0.01, 24.71) | 0.0000 | 0 (0, 0) | |||
ALOPECIA | Bisphosphonate | 1.05 (0.92, 1.21) | 1.11 (0.87, 1.55) | 0.06 | 0.01 (-0.01, 0.03) | |||
ANAEMIA | Nitrogenous | 1.16 (0.5, 2.68) | 1.13 (0.61, 2.17) | 0.01 | 0 (0, 0.01) | |||
ANAEMIA | Non_nitrogenous | 1.01 (0.43, 2.39) | 0.96 (0.5, 1.82) | 0.01 | 0 (-0.01, 0.01) | |||
ARTHRALGIA | Nitrogenous | 1.53 (1.29, 1.81) | 1.54 (1.28, 1.86) | 0.17 | 0.07 (0.04, 0.1) | 0.0000 | 0 (0, 0) | |
ARTHRALGIA | Non_nitrogenous | 1.2 (0.93, 1.58) | 0.17 | 0.03 (-0.01, 0.07) | 0.0000 | 0 (0, 0) | ||
arthropathy/arthritis | Bisphosphonate | 1.23 (0.88, 1.72) | 1.17 (0.79, 1.69) | 0.11 | 0.02 (-0.02, 0.06) | 0.09 | 0.01 (-0.02, 0.05) | |
ASPARTATE AMINOTRANSFERASE | Nitrogenous | 0.32 (0.1, 1.01) | 0.52 (0.2, 1.44) | 0.02 | -0.01 (-0.01, 0.01) | 0.0004 | 0 (0, 0) | |
ASPARTATE AMINOTRANSFERASE | Non_nitrogenous | 1.44 (0.55, 3.8) | 1.2 (0.42, 3.18) | 0.02 | 0 (-0.01, 0.04) | 0.0004 | 0 (0, 0) | |
ASTHENIA | Nitrogenous | 2.53 (0.49, 13.13) | 2 (0.43, 8.3) | 0.08 | 0.07 (-0.04, 0.33) | |||
BACK PAIN | Nitrogenous | 1.54 (1, 2.37) | 1.64 (1.08, 2.69) | 0.08 | 0.05 (0.01, 0.11) | 0.1 | 0.05 (0.01, 0.13) | |
BACK PAIN | Non_nitrogenous | 1.31 (0.79, 2.36) | 0.08 | 0.02 (-0.02, 0.09) | 0.1 | 0.03 (-0.02, 0.11) | ||
BILIRUBIN | Bisphosphonate | 0.15 (0.03, 0.83) | 0.07 (0.01, 0.58) | 0.08 | -0.07 (-0.08, -0.03) | |||
CARDIAC: CONGESTIVE HEART FAILURE | Zoledronic_acid_IV | 0.2 (0.01, 5.17) | 0.05 (0.01, 1.71) | 0.04 | -0.03 (-0.04, 0.02) | |||
CARDIAC EVENTS | Nitrogenous | 2.51 (1.52, 4.17) | 2.73 (1.33, 6.31) | 0.03 | 0.04 (0.01, 0.12) | 0.0020 | 0 (0, 0.01) | |
CARDIAC EVENTS | Non_nitrogenous | 5.22 (0.25, 109.67) | 4.35 (1.44, 13.6) | 0.03 | 0.08 (0.01, 0.25) | 0.0020 | 0.01 (0, 0.02) | |
CATARACT | Bisphosphonate | 0.84 (0.26, 2.75) | 0.44 (0.03, 1.8) | 0.0040 | 0 (0, 0) | |||
CELLULITIS | Bisphosphonate | 0.21 (0.01, 5.28) | 0.02 (0, 0.64) | 0.04 | -0.04 (-0.04, -0.01) | |||
CHEST PAIN | Bisphosphonate | 4.71 (0.22, 101.87) | 0.56 (0.04, 12.08) | 0.01 | -0.01 (-0.01, 0.12) | |||
CHILLS | Clodronate_Oral | 3.45 (0.73, 25.67) | 0.02 | 0.05 (-0.01, 0.35) | ||||
CHILLS | Ibandronate_Oral | 3.28 (0.72, 24.2) | 0.02 | 0.05 (-0.01, 0.33) | ||||
CHILLS | Zoledronic_acid_IV | 8.55 (2.26, 32.32) | 15.19 (3.96, 94.86) | 0.02 | 0.24 (0.06, 0.66) | |||
COLITIS | Nitrogenous | 0.02 (0, 1) | 0.0006 | 0 (0, 0) | 0.0004 | 0 (0, 0) | ||
COLITIS | Non_nitrogenous | 1.01 (0.06, 16.11) | 0.4 (0.01, 5.82) | 0.0006 | 0 (0, 0) | 0.0004 | 0 (0, 0) | |
constipation | Bisphosphonate | 1.06 (0.93, 1.21) | 1.03 (0.82, 1.26) | 0.42 | 0.01 (-0.05, 0.06) | |||
COUGH | Bisphosphonate | 1.99 (0.96, 4.13) | 1.81 (0.96, 3.63) | 0.02 | 0.01 (0, 0.04) | 0.12 | 0.08 (0, 0.21) | |
CPK increased | Clodronate_1_Oral | 5.04 (0.24, 105.07) | 5.48 (0.05, 3472.85) | 0.0003 | 0 (0, 0.52) | |||
DECREASED APPETITE | Nitrogenous | 0.98 (0.58, 1.67) | 0.89 (0.45, 1.92) | 0.04 | 0 (-0.02, 0.03) | |||
DEHYDRATION | Bisphosphonate | 1.18 (0.44, 3.15) | 0.91 (0.26, 3.27) | 0.0080 | 0 (-0.01, 0.02) | |||
DEPRESSION | Bisphosphonate | 0.96 (0.76, 1.2) | 0.96 (0.72, 1.32) | 0.02 | 0 (0, 0.01) | 0.1 | 0 (-0.03, 0.03) | |
DIARRHOEA | Nitrogenous | 0.99 (0.84, 1.16) | 1.1 (0.88, 1.55) | 0.11 | 0.01 (-0.01, 0.05) | 0.03 | 0 (0, 0.02) | |
DIARRHOEA | Non_nitrogenous | 3.34 (1.18, 9.45) | 1.81 (1.35, 2.74) | 0.11 | 0.07 (0.03, 0.14) | 0.03 | 0.03 (0.01, 0.05) | |
DIZZINESS | Bisphosphonate | 1.44 (0.89, 2.32) | 1.33 (0.74, 2.4) | 0.03 | 0.01 (-0.01, 0.04) | 0.09 | 0.03 (-0.02, 0.1) | |
dry mouth | Bisphosphonate | 0.55 (0.2, 1.52) | 0.4 (0.12, 1.16) | 0.04 | -0.02 (-0.04, 0.01) | |||
DYSGEUSIA | Clodronate_1_Oral | 3.02 (0.12, 74.25) | 1.53 (0.02, 566.04) | 0.0010 | 0 (0, 0.37) | |||
DYSGEUSIA | Ibandronate_3_Oral | 1.06 (0.35, 4.52) | 0.0010 | 0 (0, 0) | ||||
DYSGEUSIA | Zoledronic_acid_1_IV | 1.07 (0.85, 1.35) | 1.09 (0.46, 2.86) | 0.0010 | 0 (0, 0) | |||
DYSGEUSIA | Zoledronic_acid_2_IV | 10.1 (1.17, 87.24) | 8.53 (1.25, 119.84) | 0.0010 | 0.01 (0, 0.11) | |||
DYSPEPSIA | Clodronate | 0.44 (0.06, 3.28) | 0.04 | -0.02 (-0.04, 0.08) | ||||
DYSPEPSIA | Ibandronate | 0.47 (0.06, 3.59) | 0.04 | -0.02 (-0.04, 0.09) | ||||
DYSPEPSIA | Risedronate | 0.29 (0.03, 2.72) | 0.04 | -0.03 (-0.04, 0.06) | ||||
DYSPEPSIA | Zoledronic_acid | 0.48 (0.04, 5.46) | 0.2 (0.03, 1.51) | 0.04 | -0.03 (-0.04, 0.02) | |||
dysphagia | Bisphosphonate | 0.5 (0.11, 2.3) | 0.28 (0.04, 2.64) | 0.08 | -0.05 (-0.07, 0.1) | 0.0000 | 0 (0, 0) | |
DYSPNOEA | Nitrogenous | 1.47 (0.7, 3.11) | 1.34 (0.58, 3.19) | 0.02 | 0.01 (-0.01, 0.04) | 0.0004 | 0 (0, 0) | |
DYSPNOEA | Non_nitrogenous | 0.94 (0.38, 2.33) | 0.02 | 0 (-0.01, 0.03) | 0.0004 | 0 (0, 0) | ||
Elevated creatinine | Clodronate_Oral | 1.24 (0.18, 6.04) | 0.08 | 0.02 (-0.07, 0.27) | ||||
Elevated creatinine | Ibandronate_IV | 0.86 (0.05, 9.43) | 0.08 | -0.01 (-0.08, 0.38) | ||||
Elevated creatinine | Ibandronate_Oral | 0.78 (0.07, 4.88) | 0.08 | -0.02 (-0.08, 0.23) | ||||
Elevated creatinine | Pamidronate_IV | 0.93 (0.33, 2.64) | 0.64 (0.13, 2.39) | 0.08 | -0.03 (-0.07, 0.1) | |||
Elevated creatinine | Zoledronic_acid_IV | 1.15 (0.16, 8.36) | 0.74 (0.09, 2.63) | 0.08 | -0.02 (-0.08, 0.11) | |||
endometrial hyperplasia | Zoledronic_acid_IV | 1.12 (0.74, 1.72) | ||||||
FATIGUE | Bisphosphonate | 1.13 (1.02, 1.26) | 1.28 (1.06, 1.65) | 0.1 | 0.03 (0.01, 0.06) | 0.21 | 0.04 (0.01, 0.09) | |
FEBRILE NEUTROPENIA | Clodronate | 1.07 (0.05, 8.39) | 0.0040 | 0 (0, 0.03) | ||||
FEBRILE NEUTROPENIA | Ibandronate | 4.56 (0.36, 39.36) | 0.0040 | 0.02 (0, 0.14) | ||||
FEBRILE NEUTROPENIA | Zoledronic_acid | 0.98 (0.79, 1.23) | 0.85 (0.18, 1.28) | 0.0040 | 0 (0, 0) | |||
FEVER | Clodronate_Oral | 0.64 (0.16, 2.36) | 0.01 | 0 (-0.01, 0.02) | ||||
FEVER | Ibandronate_IV | 2.56 (0.44, 13.76) | 0.01 | 0.02 (-0.01, 0.14) | ||||
FEVER | Ibandronate_Oral | 0.49 (0.09, 2.03) | 0.01 | -0.01 (-0.01, 0.01) | ||||
FEVER | Pamidronate_IV | 1.52 (0.47, 4.92) | 4.87 (1.9, 12.62) | 0.01 | 0.05 (0.01, 0.13) | |||
FEVER | Zoledronic_acid_IV | 4.06 (3.06, 5.38) | 5.2 (2.88, 8.79) | 0.01 | 0.05 (0.02, 0.09) | |||
GGT increased | Non_nitrogenous | 5.04 (0.24, 105.07) | 4.89 (0.14, 9458.49) | 0.0003 | 0 (0, 0.74) | |||
HAND-FOOT SYNDROME | Clodronate_1_Oral | 3.02 (0.12, 74.25) | 0.0080 | |||||
HAND-FOOT SYNDROME | Zoledronic_acid_1_IV | 0.91 (0.05, 17.05) | 0.0080 | |||||
HAND-FOOT SYNDROME | Zoledronic_acid_2_IV | 2.08 (0.12, 36.73) | 0.0080 | |||||
HEADACHE | Clodronate | 0.96 (0.45, 1.78) | 0.24 | -0.01 (-0.12, 0.12) | ||||
HEADACHE | Ibandronate | 1.08 (0.59, 1.86) | 0.24 | 0.01 (-0.08, 0.13) | ||||
HEADACHE | Pamidronate | 1.77 (0.86, 4.09) | 0.24 | 0.12 (-0.03, 0.32) | ||||
HEADACHE | Risedronate | 0.91 (0.3, 2.76) | 0.24 | -0.02 (-0.15, 0.23) | ||||
HEADACHE | Zoledronic_acid | 1.19 (1.02, 1.4) | 1.48 (1.06, 2.25) | 0.24 | 0.08 (0.01, 0.18) | |||
HEPATOTOXICITY | Clodronate_Oral | 1.69 (1.05, 2.71) | 1.46 (0.78, 2.59) | 0.26 | 0.08 (-0.04, 0.22) | |||
HEPATOTOXICITY | Ibandronate_Oral | 4.27 (1.28, 14.22) | 3.39 (1.13, 11.73) | 0.26 | 0.28 (0.02, 0.54) | |||
HEPATOTOXICITY | Zoledronic_acid_IV | 1.08 (0.6, 1.95) | 1.2 (0.65, 2.28) | 0.26 | 0.04 (-0.07, 0.19) | |||
HOT FLUSHES | Bisphosphonate | 0.95 (0.82, 1.1) | 0.93 (0.78, 1.1) | 0.24 | -0.01 (-0.04, 0.02) | 0.32 | -0.02 (-0.05, 0.02) | |
HYPERGLYCAEMIA | Clodronate_1_Oral | 0.62 (0.26, 1.49) | 0.61 (0.18, 1.7) | 0.0100 | 0 (-0.01, 0.01) | |||
HYPERGLYCAEMIA | Ibandronate_3_Oral | 0.55 (0.1, 1.79) | 0.0100 | 0 (-0.01, 0.01) | ||||
HYPERGLYCAEMIA | Zoledronic_acid_1_IV | 0.68 (0.11, 2.11) | 0.0100 | 0 (-0.01, 0.01) | ||||
HYPERGLYCAEMIA | Zoledronic_acid_2_IV | 2.55 (0.99, 6.61) | 2.51 (0.68, 9.11) | 0.0100 | 0.01 (0, 0.07) | |||
HYPERTENSION | Nitrogenous | 1.04 (0.36, 3.04) | 0.97 (0.38, 2.59) | 0.02 | 0 (-0.01, 0.03) | 0.16 | 0 (-0.09, 0.17) | |
HYPERTENSION | Non_nitrogenous | 1.31 (0.49, 3.61) | 0.02 | 0.01 (-0.01, 0.04) | 0.16 | 0.04 (-0.07, 0.25) | ||
hypertonia/muscle spasms | Bisphosphonate | 1.53 (1.02, 2.3) | 1.52 (0.93, 2.81) | 0.04 | 0.02 (0, 0.07) | |||
hypoalbuminemia | Bisphosphonate | 5.04 (0.24, 105.07) | 3.28 (0.05, 301.58) | 0.0003 | 0 (0, 0.08) | |||
HYPOCALCEMIA | Clodronate | 5.56 (0.94, 37.94) | 0.04 | 0.15 (0, 0.58) | ||||
HYPOCALCEMIA | Ibandronate | 6.15 (1.16, 41.76) | 0.04 | 0.17 (0.01, 0.6) | ||||
HYPOCALCEMIA | Pamidronate | 3.23 (1.45, 7.22) | 3.18 (1.2, 8.64) | 0.04 | 0.08 (0.01, 0.23) | |||
HYPOCALCEMIA | Zoledronic_acid | 7.07 (0.87, 57.56) | 7.28 (1.36, 48.93) | 0.04 | 0.2 (0.01, 0.64) | |||
HYPOKALAEMIA | Clodronate_1_Oral | 2.36 (0.61, 9.12) | 0.01 | |||||
HYPOKALAEMIA | Zoledronic_acid_1_IV | 1.35 (0.17, 10.92) | 0.01 | |||||
HYPOKALAEMIA | Zoledronic_acid_2_IV | 0.91 (0.24, 3.43) | 0.01 | |||||
hyponatremia | Bisphosphonate | 7.06 (0.36, 136.81) | 2.94 (0.33, 3309.12) | 0.0003 | 0 (0, 0.5) | |||
Hypophosphatemia | Clodronate | 0.34 (0.01, 8.24) | 0.04 (0, 0.85) | 0.0006 | 0 (0, 0) | |||
Hypophosphatemia | Ibandronate | 0.06 (0, 1.49) | 0.0006 | 0 (0, 0) | ||||
Hypophosphatemia | Zoledronic_acid | 0.07 (0, 1.58) | 0.0006 | 0 (0, 0) | ||||
increased bone pain | Bisphosphonate | 1.73 (1.47, 2.04) | 1.79 (1.33, 2.49) | 0.11 | 0.07 (0.03, 0.13) | |||
INFECTION | Clodronate_Oral | 1.13 (0.48, 2.66) | 0.22 | 0.0009 | ||||
INFECTION | Ibandronate_Oral | 2.24 (1.18, 4.22) | 0.22 | 0.0009 | ||||
INFECTION | Zoledronic_acid_IV | 1.02 (0.88, 1.19) | 0.22 | 0.0009 | ||||
Influenza-like symptoms | Bisphosphonate | 22.18 (2.98, 164.89) | 16.09 (2.04, 207.85) | 0.03 | 0.33 (0.03, 0.85) | |||
INR increased | Clodronate_1_Oral | 0.09 (0.01, 1.65) | 0.0030 | |||||
INSOMNIA | Bisphosphonate | 1.33 (0.59, 2.98) | 1.26 (0.64, 2.81) | 0.05 | 0.01 (-0.02, 0.07) | 0.08 | 0.02 (-0.03, 0.12) | |
IRREGULAR MENSTRUATION | Bisphosphonate | 1.08 (0.5, 2.36) | 0.91 (0.31, 2.21) | 0.02 | 0 (-0.02, 0.03) | |||
ISCHAEMIC CARDIOVASCULAR DISEASE | Zoledronic_acid_IV | 5.91 (0.24, 145.97) | 3.52 (0.06, 776.16) | 0.0030 | 0.01 (0, 0.72) | |||
ISCHAEMIC CEREBROVASCULAR EVENT | Bisphosphonate | 2.41 (0.68, 8.54) | 1.55 (0.43, 6.91) | 0.0020 | 0 (0, 0.01) | |||
LEUCOCYTOPAENIA | Bisphosphonate | 1.11 (0.66, 1.9) | 0.99 (0.53, 1.99) | 0.7 | 0 (-0.15, 0.12) | |||
lipase increased | Non_nitrogenous | 9.08 (0.49, 168.86) | 12.1 (0.36, 85530.05) | 0.0003 | 0 (0, 0.96) | |||
LIVER PROBLEMS | Clodronate | 0.91 (0.61, 1.37) | 0.96 (0.48, 2.27) | 0.08 | 0 (-0.04, 0.08) | |||
LIVER PROBLEMS | Risedronate | 5.2 (0.24, 113.59) | 2.86 (0.19, 157.6) | 0.08 | 0.12 (-0.06, 0.85) | |||
LIVER PROBLEMS | Zoledronic_acid | 0.15 (0.03, 0.83) | 0.07 (0.01, 0.58) | 0.08 | -0.07 (-0.08, -0.03) | |||
LOSS OF APPETITE | Bisphosphonate | 1.36 (0.6, 3.11) | 1.06 (0.43, 2.76) | 0.0030 | 0 (0, 0.01) | |||
LYMPHOEDEMA | Zoledronic_acid | 0.97 (0.13, 7.27) | 0.75 (0.16, 3.88) | 0.27 | -0.05 (-0.21, 0.32) | |||
LYMPHOPAENIA | Bisphosphonate | 0.49 (0.15, 1.66) | 0.32 (0.05, 1.19) | 0.01 | -0.01 (-0.01, 0) | |||
menometrorrhagia | Zoledronic_acid | 2.51 (0.49, 12.97) | 2.22 (0.24, 21.14) | |||||
MOTOR NEUROPATHY | Zoledronic_acid_2_IV | 1.1 (0.68, 1.79) | 0.18 | |||||
MUCOSITIS | Bisphosphonate | 0.76 (0.26, 2.25) | 0.47 (0.09, 1.6) | 0.03 | -0.01 (-0.03, 0.02) | |||
MUSCULOSKELETAL PAIN/EVENT | Bisphosphonate | 1.33 (1.03, 1.71) | 1.35 (0.9, 2.12) | 0.11 | 0.03 (-0.01, 0.1) | 0.0004 | 0 (0, 0) | |
Nasopharyngitis | Nitrogenous | 0.89 (0.45, 1.75) | 0.86 (0.43, 1.79) | 0.08 | -0.01 (-0.04, 0.05) | |||
NAUSEA | Bisphosphonate | 1.21 (1.08, 1.35) | 1.33 (1.11, 1.63) | 0.34 | 0.07 (0.02, 0.12) | 0.05 | 0.02 (0.01, 0.03) | |
neuralgia | Nitrogenous | 0.15 (0.03, 0.83) | 0.23 (0.02, 6.16) | 0.02 | -0.01 (-0.02, 0.08) | |||
neuralgia | Non_nitrogenous | 4.03 (0.45, 36.14) | 1.82 (0.03, 23.05) | 0.02 | 0.01 (-0.02, 0.27) | |||
NEUROSENSORY PROBLEMS | Bisphosphonate | 1.23 (1.05, 1.45) | 1.29 (1.05, 1.66) | 0.1 | 0.03 (0, 0.06) | 0.0000 | 0 (0, 0) | |
NEUTROPENIA | Bisphosphonate | 0.95 (0.79, 1.15) | 0.87 (0.49, 1.25) | 0.04 | 0 (-0.02, 0.01) | |||
neutrophil count decreased | Bisphosphonate | 0.67 (0.49, 0.91) | 0.6 (0.1, 1.12) | 0.07 | -0.03 (-0.06, 0.01) | |||
OEDEMA | Nitrogenous | 1.31 (0.87, 1.95) | 1.33 (0.88, 2.13) | 0.11 | 0.03 (-0.01, 0.1) | |||
OEDEMA | Non_nitrogenous | 1.14 (0.7, 1.98) | 0.11 | 0.01 (-0.03, 0.08) | ||||
oesophagitis | Clodronate_Oral | 5.04 (0.24, 105.07) | 1.14 (0.18, 7.15) | 0.01 | 0 (-0.01, 0.07) | |||
oesophagitis | Ibandronate_Oral | 2.46 (0.77, 7.9) | 3.29 (0.84, 17.65) | 0.01 | 0.03 (0, 0.17) | |||
oesophagitis | Zoledronic_acid_IV | 0.15 (0.03, 0.83) | 0.19 (0.02, 1.28) | 0.01 | -0.01 (-0.01, 0) | |||
ORAL MUCOSITIS | Nitrogenous | 0.98 (0.85, 1.13) | 0.96 (0.59, 1.61) | |||||
OsteoNecrosis of the Jaw | Nitrogenous | 7.69 (2.31, 25.55) | 0.0050 | |||||
OTHER EYE DISORDERS | Clodronate_Oral | 1.31 (0.25, 6.33) | 0.03 | 0.01 (-0.03, 0.15) | 0.0000 | 0 (0, 0) | ||
OTHER EYE DISORDERS | Ibandronate_Oral | 0.99 (0.42, 2.34) | 0.82 (0.13, 4.71) | 0.03 | -0.01 (-0.03, 0.11) | 0.0000 | 0 (0, 0) | |
OTHER EYE DISORDERS | Pamidronate_IV | 0.65 (0.04, 8.83) | 0.03 | -0.01 (-0.03, 0.21) | 0.0000 | 0 (0, 0) | ||
OTHER EYE DISORDERS | Risedronate_Oral | 0 (0, 0.55) | 0.03 | -0.03 (-0.03, -0.02) | 0.0000 | 0 (0, 0) | ||
OTHER EYE DISORDERS | Zoledronic_acid_IV | 1.16 (0.85, 1.58) | 1 (0.34, 2.46) | 0.03 | 0 (-0.02, 0.05) | 0.0000 | 0 (0, 0) | |
pain in extremity | Nitrogenous | 2.29 (0.43, 12.16) | 1.76 (0.49, 9.82) | 0.14 | 0.08 (-0.07, 0.48) | 0.05 | 0.04 (-0.03, 0.31) | |
pain in extremity | Non_nitrogenous | 1.56 (0.41, 9.26) | 0.14 | 0.06 (-0.08, 0.46) | 0.05 | 0.03 (-0.03, 0.29) | ||
PANCREATITIS | Nitrogenous | 0.34 (0.01, 8.71) | 0.08 (0, 1.25) | 0.0006 | 0 (0, 0) | 0.0004 | 0 (0, 0) | |
PANCREATITIS | Non_nitrogenous | 5.05 (0.59, 43.24) | 1.46 (0.09, 12.17) | 0.0006 | 0 (0, 0.01) | 0.0004 | 0 (0, 0) | |
PARAESTHESIA | Nitrogenous | 0.82 (0.31, 2.13) | 0.57 (0.21, 1.83) | 0.43 | -0.13 (-0.29, 0.15) | |||
periodontal disease | Zoledronic_acid_2_IV | 15.34 (0.87, 269.36) | 10.2 (1.14, 1322.28) | |||||
periodontal disease | Zoledronic_acid_2notai_IV | 0.8 (0.21, 2.99) | 0.82 (0.14, 4.39) | |||||
phlebitis | Bisphosphonate | 1.07 (0.86, 1.33) | 1.15 (0.56, 2.56) | |||||
PNEUMONIA | Bisphosphonate | 1 (0.39, 2.54) | 0.92 (0.21, 3.03) | 0.0060 | 0 (0, 0.01) | |||
PULMONARY EMBOLUS | Zoledronic_acid_1_IV | 1.61 (0.77, 3.38) | 0.02 | |||||
renal impairment | Bisphosphonate | 1.48 (0.7, 3.13) | 1.56 (0.7, 3.55) | 0.03 | 0.02 (-0.01, 0.07) | 0.0004 | 0 (0, 0) | |
SKIN DISORDER | Bisphosphonate | 1 (0.87, 1.14) | 1.05 (0.84, 1.4) | 0.05 | 0 (-0.01, 0.02) | |||
STOMATITIS | Clodronate_1_Oral | 1 (0.26, 2.69) | 0.15 | 0 (-0.11, 0.17) | ||||
STOMATITIS | Pamidronate_2_Oral | 1.11 (0.85, 1.44) | 1.12 (0.71, 1.76) | 0.15 | 0.02 (-0.04, 0.09) | |||
STOMATITIS | Zoledronic_acid_1_IV | 1.05 (0.88, 1.26) | 0.99 (0.5, 1.45) | 0.15 | 0 (-0.07, 0.06) | |||
STOMATITIS | Zoledronic_acid_2_IV | 0.33 (0.09, 0.89) | 0.15 | -0.1 (-0.14, -0.01) | ||||
SYNCOPE | Nitrogenous | 3 (0.1, 90.96) | 1.11 (0.13, 15.35) | 0.0040 | 0 (0, 0.06) | |||
SYNCOPE | Non_nitrogenous | 1.21 (0.37, 3.97) | 0.78 (0.15, 2.97) | 0.0040 | 0 (0, 0.01) | |||
THROMBOEMBOLIC EVENTS | Clodronate | 7.27 (1.41, 33.44) | 0.02 | 0.11 (0.01, 0.38) | 0.0009 | 0.01 (0, 0.03) | ||
THROMBOEMBOLIC EVENTS | Ibandronate | 13.15 (2.36, 68.93) | 0.02 | 0.19 (0.03, 0.56) | 0.0009 | 0.01 (0, 0.06) | ||
THROMBOEMBOLIC EVENTS | Zoledronic_acid | 3.18 (1.34, 7.51) | 2.79 (0.99, 7.42) | 0.02 | 0.03 (0, 0.11) | 0.0009 | 0 (0, 0.01) | |
THROMBOPAENIA | Bisphosphonate | 0.41 (0.06, 2.79) | 0.26 (0.03, 1.35) | 0.04 | -0.03 (-0.04, 0.01) | |||
THYROID CANCER | Zoledronic_acid | 3 (0.1, 90.96) | 0.04 (0, 5.68) | 0.09 | -0.09 (-0.09, 0.27) | |||
TRAUMATIC FRACTURES | Nitrogenous | 0.95 (0.45, 1.99) | 0.87 (0.38, 1.95) | 0.0060 | 0 (0, 0.01) | |||
uterine dilation/curettage | Nitrogenous | 1.04 (0.6, 1.82) | 0.99 (0.44, 1.95) | |||||
uterine polyp | Zoledronic_acid_2_IV | 0.75 (0.26, 2.18) | 0.09 | |||||
uterine polyp | Zoledronic_acid_2notai_IV | 1.15 (0.75, 1.76) | 0.09 | |||||
VAGINAL BLEEDING | Bisphosphonate | 4.03 (0.45, 36.39) | 3.31 (0.18, 97.23) | 0.0020 | 0 (0, 0.16) | |||
VAGINAL DISCHARGE | Bisphosphonate | 0.43 (0.11, 1.72) | 0.14 (0.02, 0.52) | 0.06 | -0.06 (-0.06, -0.03) | |||
VOMITING | Nitrogenous | 1.02 (0.89, 1.18) | 1.13 (0.89, 1.88) | 0.19 | 0.02 (-0.02, 0.12) | 0.0004 | 0 (0, 0) | |
VOMITING | Non_nitrogenous | 1.67 (1.18, 2.92) | 0.19 | 0.09 (0.03, 0.22) | 0.0004 | 0 (0, 0) | ||
MOOD DISTRUBANCES | Nitrogenous | 1.24 (0.27, 5.71) | 0.88 (0.13, 4.65) |
Treatment | Direct OR | NMA OR | Baseline risk (cancer) | Risk difference (cancer) | Baseline risk (healthy) | Risk difference (healthy) | ||
MYALGIA | ||||||||
MYALGIA | Clodronate | 1.83 (0.69, 3.65) | 0.03 | 0.03 (-0.01, 0.08) | ||||
MYALGIA | Ibandronate | 2.55 (0.93, 5.54) | 0.03 | 0.05 (0, 0.13) | ||||
MYALGIA | Zoledronic_acid | 3.3 (2.06, 5.28) | 3.22 (1.65, 5.83) | 0.03 | 0.07 (0.02, 0.14) | |||
stiffness | Zoledronic_acid_IV | 4.71 (0.22, 101.87) | 3.52 (0.19, 1185.28) | 0.02 | 0.04 (-0.01, 0.93) | |||
OTHERS | ||||||||
ABDOMINAL PAIN | Nitrogenous | 2.31 (0.71, 7.55) | 2.09 (0.78, 7.33) | 0.13 | 0.11 (-0.03, 0.39) | |||
ABDOMINAL PAIN | Non_nitrogenous | 2.24 (0.77, 8.28) | 0.13 | 0.12 (-0.03, 0.42) | ||||
ALANINE AMINOTRANSFERASE | Nitrogenous | 0.53 (0.12, 2.44) | 0.76 (0.24, 2.07) | 0.0090 | 0 (-0.01, 0.01) | 0.0004 | 0 (0, 0) | |
ALANINE AMINOTRANSFERASE | Non_nitrogenous | 2.17 (0.88, 5.33) | 1.79 (0.62, 4.69) | 0.0090 | 0.01 (0, 0.03) | 0.0004 | 0 (0, 0) | |
ALKALINE PHOSPHATASE | Zoledronic_acid_1_IV | 0.45 (0.09, 2.22) | 0.15 | 0.0000 | ||||
ALKALINE PHOSPHATASE | Zoledronic_acid_2_IV | 0.26 (0.05, 1.33) | 0.15 | 0.0000 | ||||
ALOPECIA | Bisphosphonate | 1.46 (0.87, 2.43) | 1.31 (0.77, 2.27) | 0.06 | 0.02 (-0.01, 0.07) | |||
ANAEMIA | Bisphosphonate | 1.48 (0.74, 2.95) | 1.41 (0.67, 2.74) | 0.01 | 0 (0, 0.02) | |||
ARTHRALGIA | Nitrogenous | 1.37 (1, 1.88) | 1.34 (0.95, 1.94) | 0.17 | 0.04 (-0.01, 0.11) | 0.0000 | 0 (0, 0) | |
ARTHRALGIA | Non_nitrogenous | 1.06 (0.71, 1.61) | 0.17 | 0.01 (-0.04, 0.08) | 0.0000 | 0 (0, 0) | ||
arthropathy/arthritis | Clodronate | 1.17 (0.34, 2.91) | 0.11 | 0.02 (-0.07, 0.16) | 0.09 | 0.01 (-0.06, 0.13) | ||
arthropathy/arthritis | Ibandronate | 1.21 (0.24, 3.46) | 0.11 | 0.02 (-0.08, 0.19) | 0.09 | 0.02 (-0.07, 0.16) | ||
arthropathy/arthritis | Risedronate | 0 (0, 0.04) | 0.11 | -0.11 (-0.11, -0.11) | 0.09 | -0.09 (-0.09, -0.09) | ||
arthropathy/arthritis | Zoledronic_acid | 1.6 (0.91, 2.81) | 1.21 (0.44, 2.38) | 0.11 | 0.02 (-0.06, 0.12) | 0.09 | 0.02 (-0.05, 0.1) | |
ASPARTATE AMINOTRANSFERASE | Nitrogenous | 0.32 (0.1, 1.01) | 0.48 (0.2, 1.37) | 0.02 | -0.01 (-0.01, 0.01) | 0.0004 | 0 (0, 0) | |
ASPARTATE AMINOTRANSFERASE | Non_nitrogenous | 1.44 (0.55, 3.8) | 1.13 (0.46, 3.07) | 0.02 | 0 (-0.01, 0.04) | 0.0004 | 0 (0, 0) | |
ASTHENIA | Risedronate_1_Oral | NA (NA, NA) | 0.08 | |||||
ASTHENIA | Zoledronic_acid_1_IV | 0.84 (0.1, 7) | 0.08 | |||||
ASTHENIA | Zoledronic_acid_2_IV | 0.66 (0.13, 3.35) | 0.08 | |||||
BACK PAIN | Nitrogenous | 2.19 (0.78, 6.13) | 2.46 (1, 6.6) | 0.08 | 0.1 (0, 0.29) | 0.1 | 0.11 (0, 0.32) | |
BACK PAIN | Non_nitrogenous | 1.97 (0.77, 5.58) | 0.08 | 0.07 (-0.02, 0.25) | 0.1 | 0.08 (-0.02, 0.28) | ||
BILIRUBIN | Bisphosphonate | 0.15 (0.03, 0.83) | 0.07 (0.01, 0.55) | 0.08 | -0.07 (-0.08, -0.03) | |||
CARDIAC: CONGESTIVE HEART FAILURE | Zoledronic_acid | 0.2 (0.01, 5.17) | 0.06 (0.01, 1.24) | 0.04 | -0.03 (-0.04, 0.01) | |||
CARDIAC EVENTS | Clodronate_1_Oral | 5.22 (0.25, 109.67) | 7.84 (1.27, 33.46) | 0.03 | 0.15 (0.01, 0.45) | 0.0020 | 0.01 (0, 0.05) | |
CARDIAC EVENTS | Ibandronate_3_Oral | 12.18 (2.01, 59.73) | 0.03 | 0.22 (0.03, 0.6) | 0.0020 | 0.02 (0, 0.09) | ||
CARDIAC EVENTS | Risedronate_1_Oral | 0 (0, 6.6) | 0.03 | -0.03 (-0.03, 0.13) | 0.0020 | 0 (0, 0.01) | ||
CARDIAC EVENTS | Zoledronic_acid_1_IV | 1.54 (0.63, 3.72) | 1.51 (0.56, 3.99) | 0.03 | 0.01 (-0.01, 0.07) | 0.0020 | 0 (0, 0.01) | |
CARDIAC EVENTS | Zoledronic_acid_2_IV | 3.75 (0.8, 17.66) | 2.61 (0.89, 8.17) | 0.03 | 0.04 (0, 0.16) | 0.0020 | 0 (0, 0.01) | |
CARDIAC EVENTS | Zoledronic_acid_4_IV | 2.49 (0.71, 9.4) | 0.03 | 0.04 (-0.01, 0.18) | 0.0020 | 0 (0, 0.01) | ||
CATARACT | Bisphosphonate | 0.84 (0.26, 2.75) | 0.0040 | |||||
CELLULITIS | Bisphosphonate | 0.21 (0.01, 5.28) | 0.02 (0, 0.71) | 0.04 | -0.04 (-0.04, -0.01) | |||
CHEST PAIN | Bisphosphonate | 4.71 (0.22, 101.87) | 0.91 (0.05, 31.56) | 0.01 | 0 (-0.01, 0.27) | |||
CHILLS | Zoledronic_acid_1_IV | 10.35 (0.56, 190.21) | 0.02 | |||||
CHILLS | Zoledronic_acid_2_IV | 8.03 (0.94, 68.6) | 0.02 | |||||
COLITIS | Bisphosphonate | 1.01 (0.06, 16.11) | 0.22 (0, 3.07) | 0.0006 | 0 (0, 0) | 0.0004 | 0 (0, 0) | |
constipation | Bisphosphonate | 0.54 (0.22, 1.3) | 0.54 (0.24, 1.38) | 0.42 | -0.14 (-0.27, 0.08) | |||
COUGH | Nitrogenous | 2.17 (0.47, 10.08) | 1.62 (0.42, 6.74) | 0.02 | 0.01 (-0.01, 0.09) | 0.12 | 0.06 (-0.06, 0.36) | |
COUGH | Non_nitrogenous | 1.51 (0.37, 6.62) | 0.02 | 0.01 (-0.01, 0.08) | 0.12 | 0.05 (-0.07, 0.35) | ||
CPK increased | Clodronate_Oral | 5.04 (0.24, 105.07) | 4.95 (0.13, 5537.82) | 0.0003 | 0 (0, 0.63) | |||
DECREASED APPETITE | Bisphosphonate | 4.65 (0.62, 34.85) | 5.4 (0.55, 605.12) | 0.04 | 0.13 (-0.02, 0.92) | |||
DEHYDRATION | Bisphosphonate | 1.18 (0.44, 3.15) | 0.98 (0.27, 3.15) | 0.0080 | 0 (-0.01, 0.02) | |||
DEPRESSION | Clodronate_1_Oral | 0.89 (0.31, 2.6) | 0.02 | 0 (-0.01, 0.03) | 0.1 | -0.01 (-0.07, 0.13) | ||
DEPRESSION | Ibandronate_3_Oral | 0.9 (0.31, 2.67) | 0.02 | 0 (-0.01, 0.03) | 0.1 | -0.01 (-0.07, 0.13) | ||
DEPRESSION | Zoledronic_acid_1_IV | 1.83 (0.44, 7.58) | 1.07 (0.42, 3.05) | 0.02 | 0 (-0.01, 0.03) | 0.1 | 0.01 (-0.06, 0.16) | |
DEPRESSION | Zoledronic_acid_2_IV | 0.86 (0.32, 2.34) | 0.93 (0.4, 2.17) | 0.02 | 0 (-0.01, 0.02) | 0.1 | -0.01 (-0.06, 0.1) | |
DEPRESSION | Zoledronic_acid_4_IV | 1.38 (0.55, 3.51) | 0.02 | 0.01 (-0.01, 0.04) | 0.1 | 0.03 (-0.04, 0.19) | ||
DIARRHOEA | Nitrogenous | 1.53 (0.66, 3.56) | 1.82 (0.96, 3.68) | 0.11 | 0.07 (0, 0.2) | 0.03 | 0.03 (0, 0.08) | |
DIARRHOEA | Non_nitrogenous | 3.34 (1.18, 9.45) | 2.91 (1.48, 5.94) | 0.11 | 0.15 (0.04, 0.31) | 0.03 | 0.06 (0.02, 0.14) | |
DIZZINESS | Nitrogenous | 1.56 (0.61, 3.95) | 1.23 (0.49, 3.39) | 0.03 | 0.01 (-0.01, 0.06) | 0.09 | 0.02 (-0.05, 0.16) | |
DIZZINESS | Non_nitrogenous | 0.89 (0.26, 2.6) | 0.03 | 0 (-0.02, 0.04) | 0.09 | -0.01 (-0.07, 0.12) | ||
dry mouth | Bisphosphonate | 0.55 (0.2, 1.52) | 0.34 (0.07, 1.11) | 0.04 | -0.03 (-0.04, 0) | |||
DYSGEUSIA | Bisphosphonate | 7.04 (1.2, 41.3) | 6.26 (0.95, 74.5) | 0.0010 | 0.01 (0, 0.07) | |||
DYSPEPSIA | Clodronate_Oral | 0.67 (0.07, 5.45) | 0.04 | -0.01 (-0.04, 0.15) | ||||
DYSPEPSIA | Ibandronate_Oral | 0.85 (0.09, 6.76) | 0.04 | -0.01 (-0.04, 0.18) | ||||
DYSPEPSIA | Risedronate_Oral | 0.43 (0.03, 4.68) | 0.04 | -0.02 (-0.04, 0.13) | ||||
DYSPEPSIA | Zoledronic_acid_IV | 0.48 (0.04, 5.46) | 0.26 (0.03, 2.07) | 0.04 | -0.03 (-0.04, 0.04) | |||
dysphagia | Bisphosphonate | 0.5 (0.11, 2.3) | 0.25 (0.05, 2.29) | 0.08 | -0.06 (-0.07, 0.08) | 0.0000 | 0 (0, 0) | |
DYSPNOEA | Zoledronic_acid_2_IV | 9.72 (0.51, 186.7) | 0.02 | 0.0004 | ||||
Elevated creatinine | Bisphosphonate | 1.03 (0.38, 2.78) | 1.51 (0.28, 6.52) | 0.08 | 0.04 (-0.06, 0.29) | |||
FATIGUE | Clodronate_1_Oral | 1.16 (0.34, 3.14) | 0.1 | 0.01 (-0.07, 0.16) | 0.21 | 0.03 (-0.12, 0.24) | ||
FATIGUE | Ibandronate_3_Oral | 1.59 (0.48, 5.36) | 0.1 | 0.05 (-0.05, 0.28) | 0.21 | 0.09 (-0.1, 0.38) | ||
FATIGUE | Ibandronate_4_IVAndOral | 4 (0.45, 36.64) | 0.1 | 0.21 (-0.05, 0.71) | 0.21 | 0.3 (-0.1, 0.7) | ||
FATIGUE | Risedronate_1_Oral | 0.62 (0.09, 4.05) | 0.1 | -0.04 (-0.09, 0.21) | 0.21 | -0.07 (-0.18, 0.31) | ||
FATIGUE | Zoledronic_acid_1_IV | 1.94 (1.32, 2.84) | 1.9 (0.96, 3.94) | 0.1 | 0.08 (0, 0.21) | 0.21 | 0.12 (-0.01, 0.3) | |
FATIGUE | Zoledronic_acid_2_IV | 1.76 (1.14, 2.73) | 2.38 (1.22, 5.15) | 0.1 | 0.11 (0.02, 0.27) | 0.21 | 0.18 (0.04, 0.37) | |
FATIGUE | Zoledronic_acid_4_IV | 2.43 (0.98, 6.75) | 0.1 | 0.12 (0, 0.33) | 0.21 | 0.18 (0, 0.43) | ||
FEBRILE NEUTROPENIA | Clodronate | 1.77 (0.52, 6.04) | 1.42 (0.27, 6.33) | 0.0040 | 0 (0, 0.02) | |||
FEBRILE NEUTROPENIA | Ibandronate | 4.65 (0.54, 39.94) | 0.0040 | 0.02 (0, 0.14) | ||||
FEBRILE NEUTROPENIA | Zoledronic_acid | 0.27 (0.03, 2.51) | 0.35 (0.04, 3.24) | 0.0040 | 0 (0, 0.01) | |||
FEVER | Clodronate_1_Oral | 6.54 (1.84, 45.74) | 0.01 | 0.06 (0.01, 0.36) | ||||
FEVER | Ibandronate_3_Oral | 8.83 (2.48, 60.44) | 0.01 | 0.09 (0.02, 0.42) | ||||
FEVER | Zoledronic_acid_1_IV | 17.55 (4.24, 72.7) | 27.03 (10.19, 179.58) | 0.01 | 0.25 (0.1, 0.69) | |||
FEVER | Zoledronic_acid_2_IV | 34.76 (8.48, 142.55) | 30.72 (11.84, 178.43) | 0.01 | 0.27 (0.12, 0.68) | |||
FEVER | Zoledronic_acid_4_IV | 6.8 (2.23, 38.99) | 0.01 | 0.07 (0.02, 0.32) | ||||
GGT increased | Clodronate_1_Oral | 5.04 (0.24, 105.07) | 5.86 (0.18, 164076396.26) | 0.0003 | 0 (0, 1) | |||
HAND-FOOT SYNDROME | Clodronate_1_Oral | 3.02 (0.12, 74.25) | 0.0080 | |||||
HAND-FOOT SYNDROME | Zoledronic_acid_1_IV | 0.91 (0.05, 17.05) | 0.0080 | |||||
HAND-FOOT SYNDROME | Zoledronic_acid_2_IV | 2.08 (0.12, 36.73) | 0.0080 | |||||
HEADACHE | Clodronate_Oral | 1.6 (0.47, 3.18) | 0.24 | 0.1 (-0.11, 0.26) | ||||
HEADACHE | Ibandronate_Oral | 1.89 (0.64, 4.17) | 0.24 | 0.13 (-0.07, 0.33) | ||||
HEADACHE | Risedronate_Oral | 1.11 (0.26, 4.09) | 0.24 | 0.02 (-0.16, 0.32) | ||||
HEADACHE | Zoledronic_acid_IV | 2.19 (1.36, 3.52) | 2.29 (1.32, 3.93) | 0.24 | 0.18 (0.05, 0.31) | |||
HEPATOTOXICITY | Bisphosphonate | 1.42 (0.98, 2.05) | 1.31 (0.77, 2.06) | 0.26 | 0.06 (-0.05, 0.16) | |||
HOT FLUSHES | Bisphosphonate | 0.91 (0.71, 1.18) | 0.88 (0.66, 1.18) | 0.24 | -0.02 (-0.07, 0.03) | 0.32 | -0.03 (-0.08, 0.04) | |
HYPERGLYCAEMIA | Clodronate_1_Oral | 0.62 (0.26, 1.49) | 0.0100 | |||||
HYPERGLYCAEMIA | Zoledronic_acid_2_IV | 2.55 (0.99, 6.61) | 0.0100 | |||||
HYPERTENSION | Nitrogenous | 0.84 (0.21, 3.28) | 0.61 (0.15, 2.37) | 0.02 | -0.01 (-0.02, 0.02) | 0.16 | -0.06 (-0.13, 0.15) | |
HYPERTENSION | Non_nitrogenous | 0.82 (0.19, 3.29) | 0.02 | 0 (-0.01, 0.04) | 0.16 | -0.02 (-0.12, 0.22) | ||
hypertonia/muscle spasms | Bisphosphonate | 3.68 (1.12, 12.05) | 3.57 (0.94, 22.24) | 0.04 | 0.1 (0, 0.46) | |||
hypoalbuminemia | Bisphosphonate | 5.04 (0.24, 105.07) | 3.12 (0.13, 163.97) | 0.0003 | 0 (0, 0.05) | |||
HYPOCALCEMIA | Bisphosphonate | 1.6 (1.03, 2.51) | 1.5 (0.76, 2.81) | 0.04 | 0.02 (-0.01, 0.07) | |||
HYPOKALAEMIA | Nitrogenous | 1.55 (0.4, 6.09) | 1.48 (0.49, 4.38) | 0.01 | 0.01 (-0.01, 0.04) | |||
HYPOKALAEMIA | Non_nitrogenous | 2.36 (0.61, 9.12) | 1.9 (0.63, 5.67) | 0.01 | 0.01 (0, 0.05) | |||
hyponatremia | Nitrogenous | 3.19 (0.3, 238.79) | 0.0003 | 0 (0, 0.07) | ||||
hyponatremia | Non_nitrogenous | 7.06 (0.36, 136.81) | 3.03 (0.3, 232.19) | 0.0003 | 0 (0, 0.07) | |||
Hypophosphatemia | Clodronate_1_Oral | 0.34 (0.01, 8.24) | 0.0006 | |||||
increased bone pain | Bisphosphonate | 1.84 (1.37, 2.48) | 1.86 (1.15, 3.08) | 0.11 | 0.08 (0.02, 0.17) | |||
INFECTION | Bisphosphonate | 1.36 (0.93, 1.99) | 1.04 (0.23, 3.51) | 0.22 | 0.01 (-0.16, 0.28) | 0.0009 | 0 (0, 0) | |
Influenza-like symptoms | Bisphosphonate | 7.36 (0.37, 147.29) | 2.03 (0.09, 42.41) | 0.03 | 0.03 (-0.03, 0.57) | |||
INR increased | Clodronate_1_Oral | 0.09 (0.01, 1.65) | 0.0030 | |||||
INSOMNIA | Clodronate_1_Oral | 0.93 (0.35, 2.39) | 0.05 | 0 (-0.03, 0.06) | 0.08 | -0.01 (-0.05, 0.1) | ||
INSOMNIA | Ibandronate_3_Oral | 0.87 (0.32, 2.29) | 0.05 | -0.01 (-0.03, 0.05) | 0.08 | -0.01 (-0.06, 0.09) | ||
INSOMNIA | Risedronate_1_Oral | 1.23 (0.03, 27.08) | 0.05 | 0.01 (-0.05, 0.52) | 0.08 | 0.02 (-0.08, 0.63) | ||
INSOMNIA | Zoledronic_acid_1_IV | 1.83 (0.44, 7.58) | 1.13 (0.46, 2.71) | 0.05 | 0.01 (-0.02, 0.07) | 0.08 | 0.01 (-0.04, 0.12) | |
INSOMNIA | Zoledronic_acid_2_IV | 1.12 (0.41, 3.05) | 1.12 (0.47, 2.54) | 0.05 | 0.01 (-0.02, 0.06) | 0.08 | 0.01 (-0.04, 0.1) | |
INSOMNIA | Zoledronic_acid_4_IV | 0.74 (0.29, 1.8) | 0.05 | -0.01 (-0.03, 0.03) | 0.08 | -0.02 (-0.06, 0.06) | ||
IRREGULAR MENSTRUATION | Bisphosphonate | 1.08 (0.5, 2.36) | 0.92 (0.36, 2.19) | 0.02 | 0 (-0.01, 0.03) | |||
ISCHAEMIC CARDIOVASCULAR DISEASE | Zoledronic_acid | 5.91 (0.24, 145.97) | 3.71 (0.09, 1180.23) | 0.0030 | 0.01 (0, 0.8) | |||
ISCHAEMIC CEREBROVASCULAR EVENT | Bisphosphonate | 2.41 (0.68, 8.54) | 1.49 (0.4, 6.88) | 0.0020 | 0 (0, 0.01) | |||
LEUCOCYTOPAENIA | Clodronate | 1.11 (0.66, 1.9) | 1.01 (0.43, 2.03) | 0.7 | 0 (-0.2, 0.13) | |||
LEUCOCYTOPAENIA | Ibandronate | 0.75 (0.21, 1.78) | 0.7 | -0.06 (-0.37, 0.11) | ||||
LEUCOCYTOPAENIA | Risedronate | 0.12 (0, 2.39) | 0.7 | -0.48 (-0.69, 0.15) | ||||
LEUCOCYTOPAENIA | Zoledronic_acid | 0.98 (0.24, 2.2) | 0.7 | 0 (-0.34, 0.14) | ||||
lipase increased | Clodronate_Oral | 9.08 (0.49, 168.86) | 12.14 (0.45, 798708.37) | 0.0003 | 0 (0, 1) | |||
LIVER PROBLEMS | Zoledronic_acid_IV | 0.15 (0.03, 0.83) | 0.06 (0.01, 0.65) | 0.08 | -0.07 (-0.08, -0.03) | |||
LOSS OF APPETITE | Bisphosphonate | 0.8 (0.22, 3) | 0.46 (0.06, 2.41) | 0.0030 | 0 (0, 0) | |||
LYMPHOEDEMA | Bisphosphonate | 0.97 (0.13, 7.27) | 0.7 (0.15, 3.99) | 0.27 | -0.06 (-0.22, 0.32) | |||
LYMPHOPAENIA | Bisphosphonate | 0.49 (0.15, 1.66) | 0.32 (0.06, 1.16) | 0.01 | -0.01 (-0.01, 0) | |||
MOTOR NEUROPATHY | Clodronate_1_Oral | 0.67 (0.11, 4.02) | 0.18 | |||||
MOTOR NEUROPATHY | Zoledronic_acid_2_IV | 1.1 (0.68, 1.79) | 0.18 | |||||
MUCOSITIS | Bisphosphonate | 0.76 (0.26, 2.25) | 0.46 (0.03, 1.73) | 0.03 | -0.01 (-0.03, 0.02) | |||
MUSCULOSKELETAL PAIN/EVENT | Bisphosphonate | 1.2 (0.79, 1.82) | 1.26 (0.71, 2.77) | 0.11 | 0.03 (-0.03, 0.15) | 0.0004 | 0 (0, 0) | |
Nasopharyngitis | Zoledronic_acid_1_IV | 0.48 (0.14, 1.72) | 0.08 | |||||
Nasopharyngitis | Zoledronic_acid_2_IV | 1.33 (0.28, 6.38) | 0.08 | |||||
NAUSEA | Bisphosphonate | 1.23 (0.87, 1.73) | 1.31 (0.86, 2.14) | 0.34 | 0.06 (-0.03, 0.18) | 0.05 | 0.02 (-0.01, 0.06) | |
neuralgia | Clodronate_Oral | 4.03 (0.45, 36.14) | 1.96 (0.03, 21.2) | 0.02 | 0.02 (-0.02, 0.25) | |||
neuralgia | Zoledronic_acid_IV | 0.15 (0.03, 0.83) | 0.25 (0.02, 7.4) | 0.02 | -0.01 (-0.02, 0.1) | |||
NEUROSENSORY PROBLEMS | Bisphosphonate | 1.56 (1.1, 2.21) | 1.49 (1, 2.23) | 0.1 | 0.04 (0, 0.1) | 0.0000 | 0 (0, 0) | |
NEUTROPENIA | Nitrogenous | 2.04 (0.7, 5.93) | 2.33 (1, 5.43) | 0.04 | 0.05 (0, 0.15) | |||
NEUTROPENIA | Non_nitrogenous | 0.68 (0.46, 1) | 0.68 (0.36, 1.3) | 0.04 | -0.01 (-0.03, 0.01) | |||
neutrophil count decreased | Bisphosphonate | 0.67 (0.49, 0.91) | 0.62 (0.09, 1.18) | 0.07 | -0.02 (-0.06, 0.01) | |||
OEDEMA | Nitrogenous | 1.3 (0.8, 2.1) | 1.27 (0.8, 2) | 0.11 | 0.03 (-0.02, 0.09) | |||
OEDEMA | Non_nitrogenous | 1.09 (0.63, 1.85) | 0.11 | 0.01 (-0.04, 0.07) | ||||
oesophagitis | Clodronate | 5.04 (0.24, 105.07) | 1.11 (0.11, 7.43) | 0.01 | 0 (-0.01, 0.07) | |||
oesophagitis | Ibandronate | 2.46 (0.77, 7.9) | 3.25 (0.77, 15.68) | 0.01 | 0.03 (0, 0.15) | |||
oesophagitis | Zoledronic_acid | 0.15 (0.03, 0.83) | 0.19 (0.02, 1.4) | 0.01 | -0.01 (-0.01, 0) | |||
OsteoNecrosis of the Jaw | Zoledronic_acid_1_IV | 11.71 (0.65, 212.64) | 0.0050 | |||||
OTHER EYE DISORDERS | Clodronate_Oral | 0.22 (0.03, 10.62) | 0.03 | -0.03 (-0.03, 0.24) | 0.0000 | 0 (0, 0) | ||
OTHER EYE DISORDERS | Ibandronate_Oral | 0.34 (0, 24.84) | 0.03 | -0.02 (-0.03, 0.44) | 0.0000 | 0 (0, 0) | ||
OTHER EYE DISORDERS | Risedronate_Oral | 0 (0, 0.32) | 0.03 | -0.03 (-0.03, -0.02) | 0.0000 | 0 (0, 0) | ||
OTHER EYE DISORDERS | Zoledronic_acid_IV | 1.12 (0.61, 2.06) | 0.42 (0.1, 1.61) | 0.03 | -0.02 (-0.03, 0.02) | 0.0000 | 0 (0, 0) | |
pain in extremity | Bisphosphonate | 2.29 (0.43, 12.16) | 1.53 (0.42, 9.74) | 0.14 | 0.06 (-0.08, 0.48) | 0.05 | 0.03 (-0.03, 0.3) | |
PANCREATITIS | Clodronate_Oral | 5.05 (0.59, 43.24) | 1.99 (0.26, 18.61) | 0.0006 | 0 (0, 0.01) | 0.0004 | 0 (0, 0.01) | |
PANCREATITIS | Ibandronate_Oral | 0 (0, 0.14) | 0.0006 | 0 (0, 0) | 0.0004 | 0 (0, 0) | ||
PANCREATITIS | Zoledronic_acid_IV | 0.39 (0, 6.52) | 0.0006 | 0 (0, 0) | 0.0004 | 0 (0, 0) | ||
PARAESTHESIA | Zoledronic_acid_IV | 1.02 (0.25, 4.1) | 0.54 (0.14, 3.09) | 0.43 | -0.14 (-0.33, 0.27) | |||
PNEUMONIA | Bisphosphonate | 1 (0.39, 2.54) | 0.88 (0.2, 2.7) | 0.0060 | 0 (0, 0.01) | |||
PULMONARY EMBOLUS | Zoledronic_acid_1_IV | 2.69 (0.11, 67.11) | 0.02 | |||||
renal impairment | Bisphosphonate | 2 (0.63, 6.31) | 1.36 (0.34, 4.92) | 0.03 | 0.01 (-0.02, 0.11) | 0.0004 | 0 (0, 0) | |
SKIN DISORDER | Bisphosphonate | 1.6 (1.03, 2.48) | 1.48 (0.87, 2.44) | 0.05 | 0.02 (-0.01, 0.06) | |||
STOMATITIS | Zoledronic_acid_1_IV | 0.62 (0.13, 2.99) | 0.39 (0.09, 2.8) | 0.15 | -0.09 (-0.14, 0.18) | |||
STOMATITIS | Zoledronic_acid_2_IV | 0.23 (0.04, 1.2) | 0.16 (0.03, 1.22) | 0.15 | -0.13 (-0.15, 0.03) | |||
SYNCOPE | Nitrogenous | 3 (0.1, 90.96) | 1.13 (0.11, 15.9) | 0.0040 | 0 (0, 0.06) | |||
SYNCOPE | Non_nitrogenous | 1.21 (0.37, 3.97) | 0.78 (0.14, 3.31) | 0.0040 | 0 (0, 0.01) | |||
THROMBOEMBOLIC EVENTS | Clodronate | 16.15 (0.86, 206.82) | 0.02 | 0.22 (0, 0.78) | 0.0009 | 0.01 (0, 0.15) | ||
THROMBOEMBOLIC EVENTS | Ibandronate | 33.15 (1.62, 474.44) | 0.02 | 0.38 (0.01, 0.88) | 0.0009 | 0.03 (0, 0.3) | ||
THROMBOEMBOLIC EVENTS | Zoledronic_acid | 7.97 (1.4, 45.55) | 4.38 (0.53, 46.06) | 0.02 | 0.06 (-0.01, 0.46) | 0.0009 | 0 (0, 0.04) | |
THROMBOPAENIA | Zoledronic_acid_IV | 0.29 (0.01, 7.28) | 0.13 (0.01, 1.88) | 0.04 | -0.04 (-0.04, 0.04) | |||
THYROID CANCER | Zoledronic_acid | 3 (0.1, 90.96) | 0.04 (0, 2.19) | 0.09 | -0.09 (-0.09, 0.09) | |||
TRAUMATIC FRACTURES | Risedronate_1_Oral | NA (NA, NA) | 0.0060 | |||||
uterine polyp | Bisphosphonate | 3 (0.1, 90.96) | 1.57 (0.04, 123.96) | 0.09 | 0.05 (-0.09, 0.83) | |||
VAGINAL BLEEDING | Bisphosphonate | 4.03 (0.45, 36.39) | 3.24 (0.3, 339.48) | 0.0020 | 0 (0, 0.4) | |||
VAGINAL DISCHARGE | Zoledronic_acid | 0.43 (0.11, 1.72) | 0.14 (0.03, 0.54) | 0.06 | -0.05 (-0.06, -0.03) | |||
VOMITING | Nitrogenous | 4 (0.72, 22.09) | 0.19 | 0.0004 |
Should it be odds ratio, not risk difference, until we’ve discussed baseline? Discuss heterogeneity in ORs vs RDs To illustrate this, just point to forest plot ORs for homogeneity. Can we discuss het in baselines when choosing a baseline. Question whether we should be discussing risk differences here at all - as we want to make the baselines transparent. Could mention baseilne het as a motivator for picking a constant baseline. Just needs quick summary using direct-only data to motivate.
Group symptoms by class as in NMA results? Show number of studies contributing to the result in the row label
The data extracted from the 59 trials that fulfilled our criteria is shown in Supplementary Data 1. What is this?
Table 1 shows the study chars. Where is this? Should include blinding, follow up, any other data extracted
Subset analysis done for direct as well as NMA? [ suggest no! ]
notAI - indicate in supp Table 1 - is this table in there?
Appendix plots in progress. Adding more transparent direct data and model comparison
both risk ratio and risk difference?
point out which are sig in azure alone
Methods
Talk through how we did FEVER
Forest plots for selected odds ratios
Healthy women analysis